Ad26.cov2-s/immune-globulin

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 48-year-old man developed immune mediated thrombocytopenia following vaccination with Ad26.cov2-s. His thrombocytopenia did not respond to immune-globulin [not all routes and dosages stated].

The man presented to the emergency room in the USA with bilateral lower extremity pain on 26 April 2021. He had received Ad26.cov2-s vaccine on 7 April 2021 and after 11 days he experienced pain in toes that eventually progressed to his thighs bilaterally. He was a non-smoker and was not taking any medication. His platelet count was normal 2019. At current presentation, the oxygen saturation and vital signs were normal. Laboratory investigation showed decreased platelet count and increased D-dimer. All other CBC parameters were within the normal range. Additionally, SARS-CoV-2 test was negative. Venous duplex ultrasound of the lower extremities was significant for non-occlusive deep vein thrombosis in the bilateral popliteal veins extending to the gastrocnemius veins, an occlusive deep vein thrombosis of the left posterior tibial vein, as well as occlusive superficial venous thrombosis in the bilateral saphenous veins.

The man received treatment with rivaroxaban and was discharged with a two-day follow up. He had no known exposure to heparin prior. On the next day, he presented to the emergency room with pleuritic chest pain and CT scan showed multiple acute bilateral pulmonary emboli in the segmental and more proximal arteries. Hypercoagulable work-up did not reveal any abnormalities, but a peripheral smear revealed thrombocytopenia without schistocytes. Based on the findings, a presumptive diagnosis of vaccine-induced thrombotic thrombocytopenia (VITT) was made. Treatment with IV immune-globulin [IVIG] 1 g/kg was initiated for two days along with prednisone. Also, treatment with rivaroxaban was switched to argatroban. An magnetic resonance venography and angiography of the brain were unremarkable. Prior to immune-globulin, anti-PF4 enzyme-linked immunosorbent assay demonstrated a strongly positive result of 3.323 optical density units and the diagnosis of VITT was confirmed. Eventually, leg pain and chest pain resolved and the platelet count normalised on day 3 of hospitalisation. On the following day, he was discharged and the dose of prednisone was tapered off. Over the subsequent month, the dose of prednisone was tapered. He maintained persistently strong positive anti-PF4 results, but serotonin release assay was negative and D-Dimer level was normal. It was also noted that within a post-discharge, he developed recurrent thrombocytopenia. His thrombocytopenia appeared to somewhat correlate with prednisone dose adjustments and suggested an autoimmune-driven process. However, it did not respond to repeat immune-globulin. Due to negative serotonin release assay and normal D-Dimer it was assumed that there was no further ongoing platelet activation. Following repeat immune-globulin, the dose of prednisone varied and the refractory thrombocytopenia was considered as immune-mediated.